The neuronal ischemic tolerance is conditioned by the Tp53 Arg72Pro polymorphism

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of prosurvival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulatorMDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult bymodulatingmitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.This work was funded by The Instituto de Salud Carlos III grants CP14/00010 (M.D.-E.); PI15/00473 and RD12/0014/ 0007 (A.A.); CM14/00096 (ME.R.-A.); RD16/0019/0018 (C.R.); and Junta de Castilla y Leon grant BIO/SA35/15 (M.D.-E.), and the European Regional Development Fund (R.V.) was funded by the FPU program (Ministerio de Educación)

Star formation histories in mergers: the spatially resolved properties of the early-stage merger luminous infrared galaxies IC 1623 and NGC 6090

The role of major mergers in galaxy evolution is investigated through a detailed characterization of the stellar populations, ionized gas properties and star formation rates (SFR) in the early-stage merger luminous infrared galaxies (LIRGs) IC 1623 W and NGC 6090, by analysing optical integral field spectroscopy and high-resolution Hubble Space Telescope imaging. The spectra were processed with the starlight full spectral fitting code, and the emission lines measured in the residual spectra. The results are compared with non-interacting control spiral galaxies from the Calar Alto Legacy Integral Field Area survey. Merger-induced star formation is extended and recent, as revealed by the young ages (50–80 Myr) and high contributions to light of young stellar populations (50–90 per cent), in agreement with merger simulations in the literature. These early-stage mergers have positive central gradients of the stellar metallicity, with an average ∼0.6 Z⊙. Compared to non-interacting spirals, they have lower central nebular metallicity, and flatter profiles, in agreement with the gas inflow scenario. We find that they are dominated by star formation, although shock excitation cannot be discarded in some regions, where high velocity dispersion is found (170–200 km s−1). The average SFR in these early-stage mergers (∼23–32 M⊙ yr−1) is enhanced with respect to main-sequence Sbc galaxies by factors of 6–9, slightly above the predictions from classical merger simulations, but still possible in about 15 per cent of major galaxy mergers, where U/LIRGs belong

CALIFA : a diameter-selected sample for an integral field spectroscopy galaxy survey

JMA acknowledges support from the European Research Council Starting Grant (SEDmorph; P.I. V. Wild).We describe and discuss the selection procedure and statistical properties of the galaxy sample used by the Calar Alto Legacy Integral Field Area (CALIFA) survey, a public legacy survey of 600 galaxies using integral field spectroscopy. The CALIFA "mother sample" was selected from the Sloan Digital Sky Survey (SDSS) DR7 photometric catalogue to include all galaxies with an r-band isophotal major axis between 45 '' and 79 : 2 '' and with a redshift 0 : 005 M-r > -23 : 1 and over a stellar mass range between 10(9.7) and 10(11.4) M-circle dot. In particular, within these ranges, the diameter selection does not lead to any significant bias against - or in favour of - intrinsically large or small galaxies. Only below luminosities of M-r = -19 (or stellar masses <10(9.7) M-circle dot) is there a prevalence of galaxies with larger isophotal sizes, especially of nearly edge-on late-type galaxies, but such galaxies form <10% of the full sample. We estimate volume-corrected distribution functions in luminosities and sizes and show that these are statistically fully compatible with estimates from the full SDSS when accounting for large-scale structure. For full characterization of the sample, we also present a number of value-added quantities determined for the galaxies in the CALIFA sample. These include consistent multi-band photometry based on growth curve analyses; stellar masses; distances and quantities derived from these; morphological classifications; and an overview of available multi-wavelength photometric measurements. We also explore different ways of characterizing the environments of CALIFA galaxies, finding that the sample covers environmental conditions from the field to genuine clusters. We finally consider the expected incidence of active galactic nuclei among CALIFA galaxies given the existing pre-CALIFA data, finding that the final observed CALIFA sample will contain approximately 30 Sey2 galaxies.Peer reviewe

Extreme Starbursts in the Local Universe

The "Extreme starbursts in the local universe" workshop was held at the Insituto de Astrofisica de Andalucia in Granada, Spain on 21-25 June 2010. Bearing in mind the advent of a new generation of facilities such as JWST, Herschel, ALMA, eVLA and eMerlin, the aim of the workshop was to bring together observers and theorists to review the latest results. The purpose of the workshop was to address the following issues: what are the main modes of triggering extreme starbursts in the local Universe? How efficiently are stars formed in extreme starbursts? What are the star formation histories of local starburst galaxies? How well do the theoretical simulations model the observations? What can we learn about starbursts in the distant Universe through studies of their local counterparts? How important is the role of extreme starbursts in the hierarchical assembly of galaxies? How are extreme starbursts related to the triggering of AGN in the nuclei of galaxies? Overall, 41 talks and 4 posters with their corresponding 10 minutes short talks were presented during the workshop. In addition, the workshop was designed with emphasis on discussions, and therefore, there were 6 discussion sessions of up to one hour during the workshop. Here is presented a summary of the purposes of the workshop as well as a compilation of the abstracts corresponding to each of the presentations. The summary and conclusions of the workshop along with a description of the future prospects by Sylvain Veilleux can be found in the last section of this document. A photo of the assistants is included.Comment: worksho

Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A

Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N= 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [&lt;1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None

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A dynamic scale for surgical activity (DYSSA) stratification during the COVID-19 pandemic

Dear Editor, healthcare systems worldwide are facing the “Severe Acute Respiratory Syndrome CoronaVirus 2” (SARS-CoV-2) pandemic which is responsible for the COrona Virus Disease 2019 (COVID-19) 1. It was first identified in China, in December 2019 and it is responsible for the current outbreak (elevated as Public Health Emergency of International Concern and later to pandemic by the World Health Organization) 1. Due to its rapid diffusion, it is probable that confirmed or suspected COVID-19 patients will eventually need of surgery such as non-infected patients. In many centers, the only possible scenarios will be undeferrable emergency or elective surgeries 2,3. The indication for surgery should be individualized and based on a highly accurate diagnosis, multidisciplinary committees decision and considering the hospital and the affected area conditions 4. Where possible, a non-operative approach could be considered if feasible and always evaluating patient’s risk/benefit 4. Due to the important repercussions that the COVID-19 pandemic is causing, it is important to consider the different scenarios that surgeons might face in their hospitals. To provide useful and practical recommendations for surgical teams in the decision-making process, the Spanish Association of Surgery (Asociación Española de Cirujanos – AEC) established a Working Group of experts named “Surgery-AEC-COVID” 5 which developed the Dynamic Scale for Surgical Activity (DYSSA) (Table 1). It includes five phases, based on the feasibility and suitability of performing elective or emergency surgery for each hospital, that detail the progression of the COVID-19 pandemic. It is based on current literature 2-4 and on the cumulative experience from surgeons and centers after analyzing the situation internationally. In order to validate if DYSSA was a useful scale, applicable to reality, a survey was sent to the AEC and to the European Association for Endoscopic Surgeons (EAES) members. DYSSA resulted “adequate” for 86.8% of the AEC members (427 out of 492 answers) and for 89.1% of the EAES members (271 out of 304 answers) who responded to the survey. Several guidelines are useful for the general management of patients 2-4, however, the aim of the DYSSA is to provide a dynamic classification of the situation of each hospital involved in the pandemic, to be able to help surgeons in the decision-making process, both during the expansion or the restoration of the SARS-CoV-2 infection, and to optimize the available resources. The classification in phases is based on the percentage of hospitalized COVID-19 patients, with detailed recommendations associated with each phase. DYSSA allows addressing patients to the most appropriate hospital in case of resources centralization and to sort patients in the most appropriate hospitals according to the planned surgical strategy at a regional level. In our opinion, DYSSA is a valuable and useful tool to classify scenarios depending on the hospital global situation and to guide surgeons in the prioritization of the operations to perform. It is crucial to highlight that the current pandemic is an unexpected situation that rapidly and continuously evolves, so new and different solutions will have to be considered dynamically